Use of blood biomarkers to screen for obstructive sleep apnea

Figures & data

Table 1 Study population characteristics by diagnosis

Parameter	Characteristics	Total (n=264)	Non-OSA (n=43)	OSA (n=221)	p-value
Age	Age (years)	45.0 (36.0–53.0)	38.0 (34.0–47.0)	47.0 (37.0–54.0)	<0.05
Race	White	168/264 (63.6%)	31	137	0.883
	Black	40/264 (15.2%)	6	34
	Asian/Pacific Islander	29/264 (11.0%)	4	25
	Other/unknown	27/264 (10.2%)	7	20
Baseline characteristics	BMI	30.9 (28.0–36.1)	27.1 (24.3–29.8)	31.9 (28.7–37.1)	<0.05
	Neck circumference (inches)	17.0 (16.0–18.0)	16.0 (15.0–17.0)	17.0 (16.0–18.3)	<0.05
	ESS	10 (6–15)	11 (7–15)	10 (6–15)	0.601
Comorbidities	Obesity (BMI ≥30)	149/251 (59.4%)	11/31 (35.5%)	138/220 (62.7%)	<0.05
	Hypertension	95/251 (37.9%)	11/31 (35.5%)	84/220 (38.2%)	0.529
	Diabetes mellitus	30/251 (12.0%)	1/31 (3.2%)	29/220 (13.2%)	0.218

Notes: Data are expressed as median (interquartile range), or as n/N (%). p-values are shown for each characteristic. The p-value for race represents the relationship between diagnosis and all levels of the characteristic. Hypertension is defined as sustained elevation of blood pressure exceeding 140/90 mmHg, or high blood pressure requiring medication.

Abbreviations: BMI, body mass index; ESS, Epworth Sleepiness Scale; OSA, obstructive sleep apnea.

Figure 1 Probability of moderate/severe OSA by CRP and HbA1c values in combination.

Notes: When CRP was ≥0.2 mg/dL and HbA1c ≥5.7%, the probability of moderate/severe OSA was 81%. When neither marker was elevated, the probability was 37%, which was less than half that observed when both markers are elevated.
Abbreviations: CRP, C-reactive protein; OSA, obstructive sleep apnea.

Table 2 Comparison of ROC AUCs for OSA: biomarkers and clinical measures

Category	Parameter	AUC	95% CI
Biomarkers	HbA1c+CRP+EPO	0.78	0.71–0.86
	HbA1c	0.68	0.61–0.76
	CRP	0.72	0.63–0.81
	EPO	0.67	0.58–0.76
	IL-6	0.63	0.54–0.72
	Uric acid	0.60	0.51–0.70
Clinical measures	Age	0.63	0.54–0.72
	BMI	0.78	0.71–0.85
	Neck circumference	0.74	0.67–0.81
	Systolic BP	0.59	0.45–0.72
	Diastolic BP	0.51	0.40–0.62
	STOP-Bang	0.70	0.61–0.80
	Epworth Sleepiness Scale (ESS)	0.53	0.42–0.64

Abbreviations: AUC, area under the curve; BMI, body mass index; BP, blood pressure; CRP, C-reactive protein; EPO, erythropoietin; OSA, obstructive sleep apnea; ROC, receiver operating characteristic.

Figure 2 ROC curves for detection of OSA in non-obese subjects (BMI <30).

Notes: In non-obese subjects, the AUC for the combination of biomarkers (0.75) was higher than BMI (0.61), as well as the STOP-Bang (0.66) and ESS (0.56) scores.
Abbreviations: AUC, area under the curve; BMI, body mass index; BP, blood pressure; CRP, C-reactive protein; EPO, erythropoietin; ESS, Epworth Sleepiness Scale; FPF, false positive fraction; OSA, obstructive sleep apnea; ROC, receiver operating characteristic; TPF, true positive fraction.

Table 3 Measures of diagnostic test performance for key parameters

Parameter	Cutoff (≥)	Sensitivity	Specificity	PPV	NPV	LR(+)	LR(−)
HbA1c+CRP+EPO	9.95	81	60	91	39	2.06	0.31
HbA1c	5.7%	38	88	94	22	3.26	0.70
CRP	0.2 mg/dL	52	77	92	24	2.22	0.63
EPO	8 mIU/mL	66	58	89	25	1.58	0.58
BMI	30	64	78	94	30	2.93	0.46
Neck Circumference	17 in	44	93	97	25	6.36	0.60
STOP-Bang	3	91	29	87	39	1.29	0.30
STOP-Bang	5	44	84	93	23	2.73	0.67
ESS	11	53	55	86	19	1.18	0.85

Abbreviations: BMI, body mass index; CRP, C-reactive protein; EPO, erythropoietin; ESS, Epworth Sleepiness Scale; PPV, positive predictive value; NPV, negative predictive value; LR, likelihood ratio.

Table S1 Full title of each ethical review board, and its affiliated institution

Institution	Institutional Review Board
Sleep Center Orange County, Irvine, CA, USA	Western Institutional Review Board, Puyallup, WA, USA
Stanford Medical School, VA Palo Alto Health Care System Pulmonary, Critical Care and Sleep Medicine Section, Palo Alto, CA, USA	Administrative Panel on Human Subjects in Clinical Research, Stanford Institutional Review Board, Palo Alto, CA, USA
SleepMed Inc., Bogan Sleep Consultants, LLC, Columbia, SC, USA	Western Institutional Review Board, Puyallup, WA, USA
Southern California Permanente Medical Group, Sleep Medicine Department, Kaiser Permanente, Fontana Medical Center, Fontana, CA, USA	Kaiser Permanente Southern California Institutional Review Board, Pasadena, CA, USA
Brigham and Women’s Hospital, Harvard Medical School, Division of Sleep Medicine, Boston, MA, USA	Partners Human Research Committee, Somerville, MA, USA
EENA Comprehensive Neurology & Sleep Center, Boynton Beach, FL, USA	EENA Institutional Review Board, Boynton Beach, FL, USA
South Bend Medical Foundation (Laboratory Testing), New Technology and Test Development, South Bend, IN, USA	Schulman Institutional Review Board, Cincinnati, OH, USA
Medical Research Networx, LLC. (CRO), West Wareham, MA, USA	Diagnostics Institutional Review Board, Cummaquid, MA, USA